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首页> 外文期刊>Stem Cells >Zap70 functions to maintain stemness of mouse embryonic stem cells by negatively regulating Jak1/Stat3/c-Myc signaling.
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Zap70 functions to maintain stemness of mouse embryonic stem cells by negatively regulating Jak1/Stat3/c-Myc signaling.

机译：Zap70通过负调控Jak1 / Stat3 / c-Myc信号传导来维持小鼠胚胎干细胞的干性。

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摘要

Zeta-chain-associated protein kinase-70 (Zap70), a Syk family tyrosine kinase, has been reported to be present exclusively in normal T-cells, natural killer cells, and B cells, serving as a pivotal regulator of antigen-mediated receptor signaling and development. In this study, we report that Zap70 is expressed in undifferentiated mouse embryonic stem cells (mESCs) and may critically regulate self-renewal and pluripotency in mESCs. We found that Zap70 knocked-down mESCs (Zap70KD) show sustained self-renewal and defective differentiation. In addition, we present evidence that the sustained self-renewal in Zap70KD is associated with enhanced Jak/Stat3 signaling and c-Myc induction. These altered signaling appears to result from upregulated leukemia inhibitory factor receptor and downregulated src homology region 2 domain containing phosphatase 1 (SHP-1) phosphatase activity. On the basis of these results, we propose that in undifferentiated mESCs, Zap70 plays important roles in modulating the balance between self-renewal capacity and pluripotent differentiation ability as a key regulator of the Jak/Stat3/c-Myc signaling pathway.
机译：据报道，Syk家族的酪氨酸激酶Zeta链相关蛋白激酶70（Zap70）仅存在于正常T细胞，自然杀伤细胞和B细胞中，是抗原介导受体的关键调节剂。信号与发展。在这项研究中，我们报告Zap70在未分化的小鼠胚胎干细胞（mESCs）中表达，并可能在mESCs中关键性地调节自我更新和多能性。我们发现，Zap70敲除的mESC（Zap70KD）表现出持续的自我更新和有缺陷的分化。此外，我们目前的证据表明Zap70KD中的持续自我更新与增强的Jak / Stat3信号传导和c-Myc诱导有关。这些信号的改变似乎是由白血病抑制因子受体的上调和含磷酸酶1（SHP-1）磷酸酶活性的src同源区域2结构域的下调引起的。根据这些结果，我们提出，在未分化的mESC中，Zap70作为Jak / Stat3 / c-Myc信号通路的关键调节因子，在调节自我更新能力和多能分化能力之间的平衡中起着重要作用。

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